In 1987, it was estimated that 145,000 cases of colon carcinoma was diagnosed in the United States (1). Due to lack of effective systemic therapy for metastatic disease, 47% of all patients with colon cancer, and the majority of those with metastatic disease succumb to their malignancies (1). Thus far, chemotherapeutic agents have not exhibited sufficient antitumor activity to prolong the survival of patients with metastatic disease. Development of new diagnostic and therapeutic modalities is therefore of utmost importance.
The use of radioisotope labeled monoclonal antibodies as a diagnostic tool has been reported. Of the numerous monoclonal antibody studies which have been reported, the parameters defining specific tissue localization with radiolabeled monoclonal antibodies remain obscure. Detection of radioactivity over tumor sites by external scintigraphy does not always indicate specific localization (7). Mouse imaging experiments demonstrate that tissue vascularity and blood clearance of radiolabeled antibody strongly affect tissue antibody content (7). In a previous clinical trial of one antibody (8), tumor/nontumor radioactivity ratios were affected by several parameters including the time interval between antibody administration and biopsy as well as the types of normal tissue biopsied. Another issue is the antigen specificity of antibody localization. Isotype matched control antibodies are important to definitively prove that localization is specific.
These issues are addressed in this study by: 1) tissue biopsies from all patients seven days after administration of labeled antibody to document tumor and measure antibody uptake in tumor and normal (liver) tissues; 2) .sup.99m Tc HSA scans were performed in all patients to show that radioactivity in tumors was not due to vascularity of tumors (blood flow studies); and 3) a control antibody was compared to AS 33 to demonstrate that .sup.131 I-AS 33 localization was specific.